BACKGROUND: During human foetal development, the liver is the primary site of blood cell production, but this activity declines in the third trimester and postnatally as haematopoiesis shifts to bone marrow. In humans, this postnatal decline is not well characterized due to the scarcity of appropriate samples. OBJECTIVE: To characterize the effect of (i) gestational age at birth and (ii) length of survival after birth on hepatic haematopoiesis across various cell lineages involved. METHODS: Liver autopsy samples from 25 born-alive infants, predominantly extremely preterm newborns who died mainly between 1 day and 3 weeks after birth, were analysed. Haematopoiesis was characterized using immunohistochemical staining of established cell type-specific protein markers. RNA-sequencing data from our previous study using the same samples were also explored. RESULTS: Haematopoiesis negatively correlates with both the duration of prenatal development and the length of postnatal survival. The effect of these two factors varies across different haematopoietic cell lineages. Prenatally and early postnatally, erythropoietic cells dominated hepatic haematopoiesis but were rapidly suppressed within three days after birth. Granulopoietic activity declined more gradually after birth. Analysis of the gene expression data revealed the possible involvement of several transcription factors in lineage-specific regulatory mechanisms. CONCLUSION: This study enhances our understanding of the postnatal decline of hepatic haematopoiesis in human newborns, highlighting the differential regulation of erythropoiesis and granulopoiesis after birth. These factors bring new in-depth knowledge about the biological processes critical for postnatal adaptation of human newborns.

Department of Pathology 1st Faculty of Medicine Charles University General University Hospital Prague Czechia

Department of Pathology 3rd Faculty of Medicine Charles University University Hospital Kralovske Vinohrady Prague Czechia

Faculty of Science Charles University Prague Czechia

Laboratory of Adipose Tissue Biology Institute of Physiology of the Czech Academy of Sciences Prague Czechia

Metabolomics Service Laboratory Institute of Physiology of the Czech Academy of Sciences Prague Czechia

Research Unit for Rare Diseases Department of Pediatrics and Inherited Metabolic Disorders 1st Faculty of Medicine Charles University Prague Czechia

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