Gastrointestinal Tract - Liver Development - Revision history

Z8600021 at 03:49, 23 Ocak 2020

2020-01-23T03:49:29Z

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	{{Gastrointestinal Tract Links}}		{{Gastrointestinal Tract Links}}

	::[[Embryology_History\|'''Historic Embryology''']]: [[Paper - A Study of the Structural Unit of the Liver\|1906 Liver Structural Unit]] \| [[Book_-_Manual_of_Human_Embryology_17-7\|1912 Liver]] \| [[Book_-_Text-Book_of_Embryology_12#The_Development_of_the_Liver\|1921 Liver]] \| [[Book - Liver development\|2008 Liver]]		::[[Embryology_History\|'''Historic Embryology''']]: [[Paper - A Study of the Structural Unit of the Liver\|1906 Liver Structural Unit]] \| [[Book_-_Manual_of_Human_Embryology_17-7\|1912 Liver]] \| [[Paper - Functions of the liver in the embryo\|1920 Embryonic Function]] \| [[Book_-_Text-Book_of_Embryology_12#The_Development_of_the_Liver\|1921 Liver]] \| [[Paper - The embryogenesis of human bile capillaries and ducts\|1926 Bile Capillaries and Ducts]] \| [[Book - Liver development\|2008 Liver]]

	== Some Recent Findings ==		== Some Recent Findings ==

Z8600021 at 03:43, 23 Ocak 2020

2020-01-23T03:43:54Z

← Older revision		Revision as of 14:43, 23 Ocak 2020
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	{{Gastrointestinal Tract Links}}		{{Gastrointestinal Tract Links}}

	::[[Embryology_History\|'''Historic Embryology''']]:[[Book_-_Manual_of_Human_Embryology_17-7\|1912 Liver]] \| [[Book_-_Text-Book_of_Embryology_12#The_Development_of_the_Liver\|1921 Liver]] \| [[Book - Liver development\|2008 Liver]]		::[[Embryology_History\|'''Historic Embryology''']]: [[Paper - A Study of the Structural Unit of the Liver\|1906 Liver Structural Unit]] \| [[Book_-_Manual_of_Human_Embryology_17-7\|1912 Liver]] \| [[Book_-_Text-Book_of_Embryology_12#The_Development_of_the_Liver\|1921 Liver]] \| [[Book - Liver development\|2008 Liver]]

	== Some Recent Findings ==		== Some Recent Findings ==

Z8600021 at 03:42, 23 Ocak 2020

2020-01-23T03:42:26Z

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	See also {{liver histology}} showing both developmental and adult histology.		See also {{liver histology}} showing both developmental and adult histology.
			{{Liver Vignette}}
			<br>
	{{Gastrointestinal Tract Links}}		{{Gastrointestinal Tract Links}}

Z8600021 at 02:43, 16 Ocak 2020

2020-01-16T02:43:03Z

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	===Historic===		===Historic===
	{{Ref-Mall1906liver}}		{{Ref-Mall1906liver}}

			{{Ref-Severn1971}}

			{{Ref-Severn1972}}

	===Search Pubmed===		===Search Pubmed===

Z8600021 at 23:46, 12 December 2019

2019-12-12T23:46:03Z

← Older revision		Revision as of 10:46, 13 December 2019
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			* '''Decoding human fetal liver {{haematopoiesis}}'''{{#pmid:31597962\|PMID31597962}} "Definitive {{haematopoiesis}} in the fetal {{liver}} supports self-renewal and differentiation of haematopoietic stem cells and multipotent progenitors (HSC/MPPs) but remains poorly defined in humans. Here, using single-cell transcriptome profiling of approximately 140,000 liver and 74,000 skin, kidney and {{yolk sac}} cells, we identify the repertoire of human {{blood}} and {{immune}} cells during development. We infer differentiation trajectories from HSC/MPPs and evaluate the influence of the tissue microenvironment on blood and immune cell development. We reveal physiological erythropoiesis in fetal skin and the presence of mast cells, natural killer and innate lymphoid cell precursors in the {{yolk sac}}. We demonstrate a shift in the haemopoietic composition of fetal liver during gestation away from being predominantly erythroid, accompanied by a parallel change in differentiation potential of HSC/MPPs, which we functionally validate. Our integrated map of fetal liver haematopoiesis provides a blueprint for the study of paediatric blood and immune disorders, and a reference for harnessing the therapeutic potential of HSC/MPPs." {{blood}}

	* '''A human liver cell atlas reveals heterogeneity and epithelial progenitors'''{{#pmid:31292543\|PMID31292543}} "The human liver is an essential multifunctional organ. The incidence of liver diseases is rising and there are limited treatment options. However, the cellular composition of the liver remains poorly understood. Here we performed single-cell RNA sequencing of about 10,000 cells from normal liver tissue from nine human donors to construct a human liver cell atlas. Our analysis identified previously unknown subtypes of endothelial cells, {{Kupffer cell}}s, and {{hepatocyte}}s, with transcriptome-wide zonation of some of these populations. We show that the EPCAM+ population is heterogeneous, comprising hepatocyte-biased and cholangiocyte populations as well as a TROP2int progenitor population with strong potential to form bipotent liver organoids. As a proof-of-principle, we used our atlas to unravel the phenotypic changes that occur in hepatocellular carcinoma cells and in human hepatocytes and liver endothelial cells engrafted into a mouse liver. Our human liver cell atlas provides a powerful resource to enable the discovery of previously unknown cell types in normal and diseased livers."		* '''A human liver cell atlas reveals heterogeneity and epithelial progenitors'''{{#pmid:31292543\|PMID31292543}} "The human liver is an essential multifunctional organ. The incidence of liver diseases is rising and there are limited treatment options. However, the cellular composition of the liver remains poorly understood. Here we performed single-cell RNA sequencing of about 10,000 cells from normal liver tissue from nine human donors to construct a human liver cell atlas. Our analysis identified previously unknown subtypes of endothelial cells, {{Kupffer cell}}s, and {{hepatocyte}}s, with transcriptome-wide zonation of some of these populations. We show that the EPCAM+ population is heterogeneous, comprising hepatocyte-biased and cholangiocyte populations as well as a TROP2int progenitor population with strong potential to form bipotent liver organoids. As a proof-of-principle, we used our atlas to unravel the phenotypic changes that occur in hepatocellular carcinoma cells and in human hepatocytes and liver endothelial cells engrafted into a mouse liver. Our human liver cell atlas provides a powerful resource to enable the discovery of previously unknown cell types in normal and diseased livers."

Z8600021 at 15:51, 24 July 2019

2019-07-24T15:51:57Z

← Older revision		Revision as of 02:51, 25 July 2019
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	Tissue macrophages are a family of cells found in many organs: {{liver}} Kupffer cells, {{neural}} microglia, {{respiratory}} alveolar macrophages, and {{integumentary}} epidermal Langerhans cells. In the embryo, they have a common embryonic origin from yolk sac (YS) erythro-myeloid progenitors (EMPs). In the adult, they are self-maintained in tissues independently of hematopoietic stem cells (HSCs).{{#pmid:27492475\|PMID27492475}}		Tissue macrophages are a family of cells found in many organs{{#pmid:28662662\|PMID28662662}}: {{liver}} Kupffer cells, {{neural}} microglia, {{respiratory}} alveolar macrophages, and {{integumentary}} epidermal Langerhans cells. In the embryo, they have a common embryonic origin from yolk sac (YS) erythro-myeloid progenitors (EMPs). In the adult, they are self-maintained in tissues independently of hematopoietic stem cells (HSCs).{{#pmid:27492475\|PMID27492475}}

Z8600021 at 15:12, 24 July 2019

2019-07-24T15:12:47Z

← Older revision		Revision as of 02:12, 25 July 2019
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	* '''A human liver cell atlas reveals heterogeneity and epithelial progenitors'''{{#pmid:31292543\|PMID31292543}} "The human liver is an essential multifunctional organ. The incidence of liver diseases is rising and there are limited treatment options. However, the cellular composition of the liver remains poorly understood. Here we performed single-cell RNA sequencing of about 10,000 cells from normal liver tissue from nine human donors to construct a human liver cell atlas. Our analysis identified previously unknown subtypes of endothelial cells, Kupffer ~~cells~~, and ~~hepatocytes~~, with transcriptome-wide zonation of some of these populations. We show that the EPCAM+ population is heterogeneous, comprising hepatocyte-biased and cholangiocyte populations as well as a TROP2int progenitor population with strong potential to form bipotent liver organoids. As a proof-of-principle, we used our atlas to unravel the phenotypic changes that occur in hepatocellular carcinoma cells and in human hepatocytes and liver endothelial cells engrafted into a mouse liver. Our human liver cell atlas provides a powerful resource to enable the discovery of previously unknown cell types in normal and diseased livers."		* '''A human liver cell atlas reveals heterogeneity and epithelial progenitors'''{{#pmid:31292543\|PMID31292543}} "The human liver is an essential multifunctional organ. The incidence of liver diseases is rising and there are limited treatment options. However, the cellular composition of the liver remains poorly understood. Here we performed single-cell RNA sequencing of about 10,000 cells from normal liver tissue from nine human donors to construct a human liver cell atlas. Our analysis identified previously unknown subtypes of endothelial cells, {{Kupffer cell}}s, and {{hepatocyte}}s, with transcriptome-wide zonation of some of these populations. We show that the EPCAM+ population is heterogeneous, comprising hepatocyte-biased and cholangiocyte populations as well as a TROP2int progenitor population with strong potential to form bipotent liver organoids. As a proof-of-principle, we used our atlas to unravel the phenotypic changes that occur in hepatocellular carcinoma cells and in human hepatocytes and liver endothelial cells engrafted into a mouse liver. Our human liver cell atlas provides a powerful resource to enable the discovery of previously unknown cell types in normal and diseased livers."

	* '''The contributions of mesoderm-derived cells in liver development'''{{#pmid:30193996\|PMID30193996}} "The liver is an indispensable organ for metabolism and drug detoxification. The liver consists of endoderm-derived hepatobiliary lineages and various mesoderm-derived cells, and interacts with the surrounding tissues and organs through the ventral mesentery. Liver development, from hepatic specification to liver maturation, requires close interactions with mesoderm-derived cells, such as mesothelial cells, hepatic stellate cells, mesenchymal cells, liver sinusoidal endothelial cells and hematopoietic cells. These cells affect liver development through precise signaling events and even direct physical contact. Through the use of new techniques, emerging studies have recently led to a deeper understanding of liver development and its related mechanisms, especially the roles of mesodermal cells in liver development. Based on these developments, the current protocols for in vitro hepatocyte-like cell induction and liver-like tissue construction have been optimized and are of great importance for the treatment of liver diseases. Here, we review the roles of mesoderm-derived cells in the processes of liver development, hepatocyte-like cell induction and liver-like tissue construction."		* '''The contributions of mesoderm-derived cells in liver development'''{{#pmid:30193996\|PMID30193996}} "The liver is an indispensable organ for metabolism and drug detoxification. The liver consists of endoderm-derived hepatobiliary lineages and various mesoderm-derived cells, and interacts with the surrounding tissues and organs through the ventral mesentery. Liver development, from hepatic specification to liver maturation, requires close interactions with mesoderm-derived cells, such as mesothelial cells, hepatic stellate cells, mesenchymal cells, liver sinusoidal endothelial cells and hematopoietic cells. These cells affect liver development through precise signaling events and even direct physical contact. Through the use of new techniques, emerging studies have recently led to a deeper understanding of liver development and its related mechanisms, especially the roles of mesodermal cells in liver development. Based on these developments, the current protocols for in vitro hepatocyte-like cell induction and liver-like tissue construction have been optimized and are of great importance for the treatment of liver diseases. Here, we review the roles of mesoderm-derived cells in the processes of liver development, hepatocyte-like cell induction and liver-like tissue construction."
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	== Kupffer Cells ==		== Kupffer Cells ==

	Kupffer Cells are a population of tissue macrophages found in the lumen of hepatic sinusoids, their role is endocytic against blood-borne materials entering the liver.		Kupffer Cells are a population of tissue macrophages found in the lumen of hepatic sinusoids, their role is endocytic acting against blood-borne materials entering the liver.

	Primordial (primitive) macrophages arise in the yolk sac and then differentiate into fetal macrophages, either of these enter the blood and migrate into the developing liver.{{#pmid:15057601\|PMID15057601}}		Primordial (primitive) macrophages arise in the yolk sac and then differentiate into fetal macrophages, either of these enter the blood and migrate into the developing liver.{{#pmid:15057601\|PMID15057601}}


	Kupffer ~~Cells image~~		Tissue macrophages are a family of cells found in many organs: {{liver}} Kupffer cells, {{neural}} microglia, {{respiratory}} alveolar macrophages, and {{integumentary}} epidermal Langerhans cells. In the embryo, they have a common embryonic origin from yolk sac (YS) erythro-myeloid progenitors (EMPs). In the adult, they are self-maintained in tissues independently of hematopoietic stem cells (HSCs).{{#pmid:27492475\|PMID27492475}}

Z8600021 at 04:05, 24 July 2019

2019-07-24T04:05:23Z

← Older revision		Revision as of 15:05, 24 July 2019
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	The fetal liver also has an endocrine role by 16-hydroxylation, that results in estriol being the major estrogen type produced in late human pregnancy.		The fetal liver also has an endocrine role by 16-hydroxylation, that results in estriol being the major estrogen type produced in late human pregnancy.

	A recent molecular study has shown that within the [[~~Liver_Development~~#Adult Liver Cells\|adult liver]] at least 20 discrete cell populations exist these include: hepatocytes, endothelial cells, cholangiocytes, hepatic stellate cells, B cells, conventional and non-conventional T cells, NK-like cells, and distinct intrahepatic monocyte/macrophage populations.{{#pmid:30348985\|PMID30348985}}		A recent molecular study has shown that within the [[Gastrointestinal Tract - Liver Development#Adult Liver Cells\|adult liver]] at least 20 discrete cell populations exist these include: hepatocytes, endothelial cells, cholangiocytes, hepatic stellate cells, B cells, conventional and non-conventional T cells, NK-like cells, and distinct intrahepatic monocyte/macrophage populations.{{#pmid:30348985\|PMID30348985}}

Z8600021 at 04:04, 24 July 2019

2019-07-24T04:04:55Z

← Older revision		Revision as of 15:04, 24 July 2019
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	The fetal liver also has an endocrine role by 16-hydroxylation, that results in estriol being the major estrogen type produced in late human pregnancy.		The fetal liver also has an endocrine role by 16-hydroxylation, that results in estriol being the major estrogen type produced in late human pregnancy.

	A recent molecular study has shown that within the [[Liver_Development#~~Adult_Liver_Cells~~\|adult liver]] at least 20 discrete cell populations exist these include: hepatocytes, endothelial cells, cholangiocytes, hepatic stellate cells, B cells, conventional and non-conventional T cells, NK-like cells, and distinct intrahepatic monocyte/macrophage populations.{{#pmid:30348985\|PMID30348985}}		A recent molecular study has shown that within the [[Liver_Development#Adult Liver Cells\|adult liver]] at least 20 discrete cell populations exist these include: hepatocytes, endothelial cells, cholangiocytes, hepatic stellate cells, B cells, conventional and non-conventional T cells, NK-like cells, and distinct intrahepatic monocyte/macrophage populations.{{#pmid:30348985\|PMID30348985}}

Z8600021 at 03:58, 24 July 2019

2019-07-24T03:58:09Z

← Older revision		Revision as of 14:58, 24 July 2019
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	* '''Molecular regulation of mammalian hepatic architecture'''{{#pmid:30797519\|PMID30797519}} "The essential liver exocrine and endocrine functions require a precise spatial arrangement of the hepatic lobule consisting of the central vein, portal vein, hepatic artery, intrahepatic bile duct system, and hepatocyte zonation. This allows blood to be carried through the liver parenchyma sampled by all hepatocytes and bile produced by the hepatocytes to be carried out of the liver through the intrahepatic bile duct system composed of cholangiocytes. The molecular orchestration of multiple signaling pathways and epigenetic factors is required to set up lineage restriction of the bipotential hepatoblast progenitor into the hepatocyte and cholangiocyte cell lineages, and to further refine cell fate heterogeneity within each cell lineage reflected in the functional heterogeneity of hepatocytes and cholangiocytes. In addition to the complex molecular regulation, there is a complicated morphogenetic choreography observed in building the refined hepatic epithelial architecture. Given the multifaceted molecular and cellular regulation, it is not surprising that impairment of any of these processes can result in acute and chronic hepatobiliary diseases. To enlighten the development of potential molecular and cellular targets for therapeutic options, an understanding of how the intricate hepatic molecular and cellular interactions are regulated is imperative. Here, we review the signaling pathways and epigenetic factors regulating hepatic cell lineages, fates, and epithelial architecture."		* '''Molecular regulation of mammalian hepatic architecture'''{{#pmid:30797519\|PMID30797519}} "The essential liver exocrine and endocrine functions require a precise spatial arrangement of the hepatic lobule consisting of the central vein, portal vein, hepatic artery, intrahepatic bile duct system, and hepatocyte zonation. This allows blood to be carried through the liver parenchyma sampled by all hepatocytes and bile produced by the hepatocytes to be carried out of the liver through the intrahepatic bile duct system composed of cholangiocytes. The molecular orchestration of multiple signaling pathways and epigenetic factors is required to set up lineage restriction of the bipotential hepatoblast progenitor into the hepatocyte and cholangiocyte cell lineages, and to further refine cell fate heterogeneity within each cell lineage reflected in the functional heterogeneity of hepatocytes and cholangiocytes. In addition to the complex molecular regulation, there is a complicated morphogenetic choreography observed in building the refined hepatic epithelial architecture. Given the multifaceted molecular and cellular regulation, it is not surprising that impairment of any of these processes can result in acute and chronic hepatobiliary diseases. To enlighten the development of potential molecular and cellular targets for therapeutic options, an understanding of how the intricate hepatic molecular and cellular interactions are regulated is imperative. Here, we review the signaling pathways and epigenetic factors regulating hepatic cell lineages, fates, and epithelial architecture."

	* '''The fate of the vitelline and umbilical veins during the development of the human liver'''{{#pmid:28786203\|PMID28786203}} "Differentiation of endodermal cells into hepatoblasts is well studied, but the remodeling of the vitelline and umbilical veins during liver development is less well understood. We compared human embryos between 3 and 10 weeks of development with pig and mouse embryos at comparable stages, . ...We found no evidence for large-scale fragmentation of embryonic veins as claimed by the 'vestigial' theory. Instead and in agreement with the 'lineage' theory, the vitelline and umbilical veins remained temporally identifiable inside the liver after being engulfed by hepatoblasts. In agreement with the 'hemodynamic' theory, the left-right shunts develop de novo."
	\|}		\|}
	{\| class="wikitable mw-collapsible mw-collapsed"		{\| class="wikitable mw-collapsible mw-collapsed"
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	\|-		\|-
	\| {{Older papers}}		\| {{Older papers}}
			* '''The fate of the vitelline and umbilical veins during the development of the human liver'''{{#pmid:28786203\|PMID28786203}} "Differentiation of endodermal cells into hepatoblasts is well studied, but the remodeling of the vitelline and umbilical veins during liver development is less well understood. We compared human embryos between 3 and 10 weeks of development with pig and mouse embryos at comparable stages, . ...We found no evidence for large-scale fragmentation of embryonic veins as claimed by the 'vestigial' theory. Instead and in agreement with the 'lineage' theory, the vitelline and umbilical veins remained temporally identifiable inside the liver after being engulfed by hepatoblasts. In agreement with the 'hemodynamic' theory, the left-right shunts develop de novo."

	* '''A single-cell transcriptomic analysis reveals precise pathways and regulatory mechanisms underlying hepatoblast differentiation'''{{#pmid:28681484\|PMID28681484}} "How bipotential hepatoblasts differentiate into hepatocytes and cholangiocytes remains unclear. Here, using single-cell transcriptomic analysis of hepatoblasts, hepatocytes, and cholangiocytes sorted from embryonic day 10.5 (E10.5) to E17.5 mouse embryos, we found that hepatoblast-to-hepatocyte differentiation occurred gradually and followed a linear default pathway. As more cells became fully differentiated hepatocytes, the number of proliferating cells decreased. Surprisingly, proliferating and quiescent hepatoblasts exhibited homogeneous differentiation states at a given developmental stage. This unique feature enabled us to combine single-cell and bulk-cell analyses to define the precise timing of the hepatoblast-to-hepatocyte transition, which occurs between E13.5 and E15.5. In contrast to hepatocyte development at almost all levels, hepatoblast-to-cholangiocyte differentiation underwent a sharp detour from the default pathway. New cholangiocyte generation occurred continuously between E11.5 and E14.5, but their maturation states at a given developmental stage were heterogeneous. Even more surprising, the number of proliferating cells increased as more progenitor cells differentiated into mature cholangiocytes. Based on an observation from the single-cell analysis, we also discovered that the protein kinase C/mitogen-activated protein kinase signaling pathway promoted cholangiocyte maturation. CONCLUSION: Our studies have defined distinct pathways for hepatocyte and cholangiocyte development in vivo, which are critically important for understanding basic liver biology and developing effective strategies to induce stem cells to differentiate toward specific hepatic cell fates in vitro.		* '''A single-cell transcriptomic analysis reveals precise pathways and regulatory mechanisms underlying hepatoblast differentiation'''{{#pmid:28681484\|PMID28681484}} "How bipotential hepatoblasts differentiate into hepatocytes and cholangiocytes remains unclear. Here, using single-cell transcriptomic analysis of hepatoblasts, hepatocytes, and cholangiocytes sorted from embryonic day 10.5 (E10.5) to E17.5 mouse embryos, we found that hepatoblast-to-hepatocyte differentiation occurred gradually and followed a linear default pathway. As more cells became fully differentiated hepatocytes, the number of proliferating cells decreased. Surprisingly, proliferating and quiescent hepatoblasts exhibited homogeneous differentiation states at a given developmental stage. This unique feature enabled us to combine single-cell and bulk-cell analyses to define the precise timing of the hepatoblast-to-hepatocyte transition, which occurs between E13.5 and E15.5. In contrast to hepatocyte development at almost all levels, hepatoblast-to-cholangiocyte differentiation underwent a sharp detour from the default pathway. New cholangiocyte generation occurred continuously between E11.5 and E14.5, but their maturation states at a given developmental stage were heterogeneous. Even more surprising, the number of proliferating cells increased as more progenitor cells differentiated into mature cholangiocytes. Based on an observation from the single-cell analysis, we also discovered that the protein kinase C/mitogen-activated protein kinase signaling pathway promoted cholangiocyte maturation. CONCLUSION: Our studies have defined distinct pathways for hepatocyte and cholangiocyte development in vivo, which are critically important for understanding basic liver biology and developing effective strategies to induce stem cells to differentiate toward specific hepatic cell fates in vitro.

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	! Summary Cell Map of the Adult Human Liver		! Summary Cell Map of the Adult Human Liver
	\|-		\|-
	\| This study{{#pmid:30348985\|PMID30348985}} has shown ~~that within~~ the adult liver at least 20 discrete cell populations exist ~~these~~ include: hepatocytes, endothelial cells, cholangiocytes, hepatic stellate cells, B cells, conventional and non-conventional T cells, NK-like cells, and distinct intrahepatic monocyte/macrophage populations.		\| This study{{#pmid:30348985\|PMID30348985}} has shown in the adult human liver at least 20 discrete cell populations exist. These include: hepatocytes, endothelial cells, cholangiocytes, hepatic stellate cells, B cells, conventional and non-conventional T cells, NK-like cells, and distinct intrahepatic monocyte/macrophage populations.
	<br>		<br><br>
	* Parenchymal cells - hepatocytes		* Parenchymal cells - hepatocytes
	* Non-parenchymal cells - endothelial cells, cholangiocytes, macrophages, hepatic stellate cells, and liver infiltrating lymphocytes- including B cells, αβ and γδ, T cells, and NK cells		* Non-parenchymal cells - endothelial cells, cholangiocytes, macrophages, hepatic stellate cells, and liver infiltrating lymphocytes- including B cells, αβ and γδ, T cells, and NK cells
			<br>
	Non-inflammatory macrophages are labeled ∗Kupffer cells based on their transcriptional similarity to mouse KC. The location of B cells, plasma cells, T cells, and NK cells has yet to be confirmed by immunohistochemical staining of these populations in situ so their location in this schematic is not representative of their zonated distribution.(text modified from original figure legend)		Non-inflammatory macrophages are labeled ∗Kupffer cells based on their transcriptional similarity to mouse KC. The location of B cells, plasma cells, T cells, and NK cells has yet to be confirmed by immunohistochemical staining of these populations in situ so their location in this schematic is not representative of their zonated distribution.(text modified from original figure legend)
	\| [[File:Adult human liver cells.jpg\|600px]]		\| [[File:Adult human liver cells.jpg\|600px]]